{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:28:26Z","timestamp":1760149706999,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["AI142523","W81X-WH-20-1-0508"],"award-info":[{"award-number":["AI142523","W81X-WH-20-1-0508"]}]},{"name":"Department of Defense Tick-borne Disease Research Program Grant","award":["AI142523","W81X-WH-20-1-0508"],"award-info":[{"award-number":["AI142523","W81X-WH-20-1-0508"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Previous studies of mice infected with Babesia microti have shown that a single dose of tafenoquine administered orally is extremely effective at decreasing microscopically detectable parasitemia. However, a critical limitation of studies to date is the lack of data concerning the plasma levels of tafenoquine that are needed to treat babesiosis. In the current study, we begin to address this gap by examining the plasma levels of tafenoquine associated with the rapid reduction of B. microti patent parasitemia in a mouse model of babesiosis. In the current study, we infected BALB\/c mice with 1 \u00d7 107\u00a0B. microti-infected red blood cells. Two days post-infection, mice were treated with 20 mg\/kg of tafenoquine succinate or vehicle control administered orally by gavage. Parasitemia and plasma levels of tafenoquine were evaluated every 24 h post-treatment for 96 h. This allowed us to correlate blood plasma levels of tafenoquine with reductions in parasitemia in treated mice. Consistent with previous studies, a single oral dose of 20 mg\/kg tafenoquine resulted in a rapid reduction in parasitemia. Plasma levels of tafenoquine 24 h post-administration ranged from 347 to 503 ng\/mL and declined thereafter. This blood plasma tafenoquine level is similar to that achieved in humans using the current FDA-approved dose for the prevention of malaria.<\/jats:p>","DOI":"10.3390\/pathogens12091113","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T11:31:18Z","timestamp":1693481478000},"page":"1113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Blood Levels of Tafenoquine following a Single Oral Dosage in BALBc Mice with Acute Babesia microti Infection That Resulted in Rapid Clearance of Microscopically Detectable Parasitemia"],"prefix":"10.3390","volume":"12","author":[{"given":"Dana G.","family":"Mordue","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Synthia J.","family":"Hale","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William E.","family":"Dennis","sequence":"additional","affiliation":[{"name":"Walter Reed Army Institute of Research, Experimental Therapeutics Branch, Department of Drug Development, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chau V.","family":"Vuong","sequence":"additional","affiliation":[{"name":"Walter Reed Army Institute of Research, Experimental Therapeutics Branch, Department of Drug Development, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu-Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[{"name":"General Nutraceutical Technology, LLC, Elmsford, NY 10523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary P.","family":"Wormser","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, New York Medical College, Valhalla, NY 10520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1111\/j.1537-2995.2009.02429.x","article-title":"Transfusion-transmitted babesiosis in the United States: Summary of a workshop","volume":"49","author":"Gubernot","year":"2009","journal-title":"Transfusion"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kumar, A., O\u2019Bryan, J., and Krause, P.J. (2021). The global emergence of human babesiosis. Pathogens, 10.","DOI":"10.3390\/pathogens10111447"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Young, K.M., Corrin, T., Wilhelm, B., Uhland, C., Greig, J., Mascarenhas, M., and Waddell, L.A. (2019). Zoonotic babesia: A scoping review of the global evidence. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0226781"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Scott, J.D., Sajid, M.S., Pascoe, E.L., and Foley, J.E. (2021). Detection of Babesia odocoilei in humans with babesiosis symptoms. Diagnostics, 11.","DOI":"10.3390\/diagnostics11060947"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Renard, I., and Ben Mamoun, C. (2021). Treatment of human babesiosis: Then and now. Pathogens, 10.","DOI":"10.3390\/pathogens10091120"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.1128\/IAI.69.6.3782-3790.2001","article-title":"Molecular basis for variable expression of merozoite surface antigen gp45 among American isolates of Babesia bigemina","volume":"69","author":"Fisher","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1093\/cid\/cix216","article-title":"Possible transfusion-transmitted Babesia divergens-like\/MO-1 infection in an Arkansas patient","volume":"64","author":"Burgess","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"509","DOI":"10.7326\/0003-4819-155-8-201110180-00362","article-title":"Transfusion-associated babesiosis in the United States: A description of cases","volume":"155","author":"Herwaldt","year":"2011","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1128\/CMR.00022-10","article-title":"Transfusion-transmitted Babesia spp.: Bull\u2019s-eye on Babesia microti","volume":"24","author":"Leiby","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/cid\/ciab050","article-title":"Clinical practice guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on diagnosis and management of babesiosis","volume":"72","author":"Krause","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1056\/NEJMra1202018","article-title":"Human babesiosis","volume":"366","author":"Vannier","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1056\/NEJM199807163390304","article-title":"Persistent parasitemia after acute babesiosis","volume":"339","author":"Krause","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1086\/525852","article-title":"Persistent and relapsing babesiosis in immunocompromised patients","volume":"46","author":"Krause","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bloch, E.M., Kumar, S., and Krause, P.J. (2019). Persistence of Babesia microti infection in humans. Pathogens, 8.","DOI":"10.3390\/pathogens8030102"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1080\/14787210.2020.1752193","article-title":"Management strategies for human babesiosis","volume":"18","author":"Smith","year":"2020","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.diagmicrobio.2016.02.016","article-title":"Persistence of babesiosis for >2 years in a patient on rituximab for rheumatoid arthritis","volume":"85","author":"Raffalli","year":"2016","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"ofado97","DOI":"10.1093\/ofid\/ofad097","article-title":"Babesia microti variant with multiple resistance mutations detected in an immunocompromised patient receiving atovaquone prophylaxis","volume":"10","author":"Holbrook","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1093\/cid\/cix477","article-title":"Clinical and molecular evidence of atovaquone and azithromycin resistance in relapsed Babesia microti infection associated with Rituximab and chronic lymphocytic leukemia","volume":"65","author":"Simon","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1086\/649859","article-title":"Emergence of resistance to azithromycin-atovaquone in immunocompromised patients with Babesia microti infection","volume":"50","author":"Wormser","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.15585\/mmwr.mm6846a4","article-title":"Guidance for using tafenoquine for prevention and anti-relapse therapy for malaria","volume":"68","author":"Haston","year":"2019","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1080\/14740338.2021.1859476","article-title":"Tafenoquine: A toxicity overview","volume":"20","author":"Chu","year":"2021","journal-title":"Expert Opin Drug Saf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s40265-018-0979-2","article-title":"Tafenoquine: First global approval","volume":"78","author":"Frampton","year":"2018","journal-title":"Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1093\/cid\/ciad075","article-title":"Characterizing the blood-stage antimalarial activity of tafenoquine in healthy volunteers experimentally infected With Plasmodium falciparum","volume":"76","author":"Barber","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5344","DOI":"10.1128\/AAC.00790-10","article-title":"Tafenoquine, an antiplasmodial 8-aminoquinoline, targets leishmania respiratory complex III and induces apoptosis","volume":"54","author":"Carvalho","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e83433","DOI":"10.7554\/eLife.83433","article-title":"The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis","volume":"11","author":"Watson","year":"2022","journal-title":"eLife"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/milmed\/usaa468","article-title":"Walter Reed Army Institute of Research (WRAIR): Fifty years of achievements that impact science and society","volume":"186","author":"Alving","year":"2021","journal-title":"Mil. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1128\/AAC.41.1.91","article-title":"Evaluation of selected antiprotozoal drugs in the Babesia microti-hamster model","volume":"41","author":"Marley","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1093\/infdis\/jiz119","article-title":"Could the drug tafenoquine revolutionize treatment of Babesia microti infection?","volume":"220","author":"Mordue","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e0020421","DOI":"10.1128\/AAC.00204-21","article-title":"Tafenoquine Is a promising drug candidate for the treatment of babesiosis","volume":"65","author":"Liu","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/cid\/ciac473","article-title":"Broad antimicrobial resistance in a case of relapsing babesiosis successfully treated with Tafenoquine","volume":"76","author":"Rogers","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e01460","DOI":"10.1016\/j.idcr.2022.e01460","article-title":"Use of tafenoquine to treat a patient with relapsing babesiosis with clinical and molecular evidence of resistance to azithromycin and atovaquone","volume":"27","author":"Marcos","year":"2022","journal-title":"IDCases"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Prasad, P.J., and Wormser, G.P. (2022). Failure of an approximately six week course of Tafenoquine to completely eradicate Babesia microti infection in an immunocompromised patient. Pathogens, 11.","DOI":"10.3390\/pathogens11091051"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"256","DOI":"10.2307\/3277582","article-title":"The \u201cGray\u201d strain of Babesia microti from a human case established in laboratory animals","volume":"56","author":"Gleason","year":"1970","journal-title":"J. Parasitol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/1475-2875-13-141","article-title":"Assessment of the prophylactic activity and pharmacokinetic profile of oral tafenoquine compared to primaquine for inhibition of liver stage malaria infections","volume":"13","author":"Li","year":"2014","journal-title":"Malar. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102211","DOI":"10.1016\/j.tmaid.2021.102211","article-title":"Long-term safety of the tafenoquine antimalarial chemoprophylaxis regimen: A 12-month, randomized, double-blind, placebo-controlled trial","volume":"45","author":"Martidis","year":"2022","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1128\/AAC.01183-06","article-title":"Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects","volume":"51","author":"Charles","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1093\/infdis\/jiac181","article-title":"Babesia duncani as a model organisms to study development, virulence, and drug susceptibility of intraerythrocytic parasites in vitro and in vivo","volume":"226","author":"Pal","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"ofad391","DOI":"10.1093\/ofid\/ofad391","article-title":"Relapsing babesiosis with molecular evidence of resistance to certain antimicrobials commonly used to treat Babesia microti infections","volume":"10","author":"Marcos","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.parint.2014.12.006","article-title":"The efficacy of artemisinin, artemether, and lumefantrine against Babesia gibsoni in vitro","volume":"64","author":"Iguchi","year":"2015","journal-title":"Parasitol. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1084\/jem.20151519","article-title":"Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone","volume":"213","author":"Lawres","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1186\/s13071-020-04235-7","article-title":"Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo","volume":"13","author":"Carvalho","year":"2020","journal-title":"Parasit. Vectors"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/9\/1113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:43:35Z","timestamp":1760129015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/9\/1113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,31]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["pathogens12091113"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12091113","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2023,8,31]]}}}